SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases.

SAMHD1 is not localized in dot-like structures under DNA double-strand break induction in HeLa cells.

study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.

Studies of the phosphomimetic and tetramerization-defective mutants of SAMHD1 reveal poor correlation between tetramerization propensity and dNTPase activity observed in vitro and the ability of the proteins to deplete cellular dNTPs and to restrict retroviral restriction. These results suggest that enzymatic activity of SAMHD1 may be subject to additional cellular regulatory mechanisms that have not yet been elucidated.

Upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3.

These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of reverse transcription (RT)that acts independently of dNTP concentrations and is specific to resting CD4 T cells.

results indicate that the RXL motif is critical for tetramer formation, dNTPase activity, and HIV-1 restriction. These findings help us understand SAMHD1 interactions with other host proteins and the mechanisms regulating SAMHD1 structure and functions in cells.

These results suggest that SAMHD1 is a relevant restriction factor for HBV and restricts reverse transcription through its dNTPase activity

SAMHD1 may constitute a promising target to improve a wide range of therapies for both hematological and non-haematological malignancies.

Study demonstrates a consistent resistance profile to PARPi and a unique cross-resistance profile to non-PARPi drugs in different PARPi-resistant U251 glioblastoma cells and reveals 53BP1 loss and SAMHD1 overexpression as the primary mechanisms responsible for their resistance to PARPi and Ara-C, respectively.

Study identify three critical cysteine residues of SAMHD1 (Cys341, Cys350, and Cys522) that create a ''redox switch'' through the formation of intrachain disulfide bonds to reversibly inhibit SAMHD1 tetramerization and dNTPase activity. SAMHD1 is oxidized in cells in response to proliferative signals and colocalizes with sites of protein oxidation outside of the nucleus.

Zebrafish SAM Domain and HD Domain 1 (SAMHD1) Interaktionspartner

Data suggest that zebrafish may represent a system for studying the relationship between type I interferon (IFN) signaling and a loss of deoxynucleoside triphosphate triphosphohydrolase SAMHD1 activity.

provide genetic evidence that cell-autonomous control of lentivirus infection in myeloid cells by SAMHD1 limits virus-induced production of interferons and the induction of co-stimulatory markers

These data support a model in which SAMHD1 catalytic activity is regulated through tetramer stabilization by the carboxyl-terminal tail, phosphorylation destabilizing the complexes and inactivating the enzyme. ISF2 may serve to reduce the dNTP pool to very low levels as a means of restricting virus replication.

SAMHD1 can restrict lentiviruses in vivo and that nucleotide starvation is an evolutionarily conserved antiviral mechanism.

there are several Vpx residues required for SAMHD1 degradation

Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication

SAMHD1 Protein Überblick

Protein Überblick

This gene may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. Mutations in this gene have been associated with Aicardi-Goutieres syndrome.